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Related Concept Videos

Channel Rhodopsins01:11

Channel Rhodopsins

Most organisms use photoreceptors to sense and respond to light. Examples of photoreceptors include bacteriorhodopsins and bacteriophytochromes in some bacteria, phytochromes in plants, and rhodopsins in the photoreceptor cells of the vertebral retina. The light-sensitive property of these receptors is because of the bound chromophores, such as bilin in the phytochromes and retinal in the rhodopsins.
Rhodopsins belong to the family of cell surface proteins called G-protein coupled receptors,...

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Electromechanical Assessment of Optogenetically Modulated Cardiomyocyte Activity
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Computational optogenetics: empirically-derived voltage- and light-sensitive channelrhodopsin-2 model.

John C Williams1, Jianjin Xu, Zhongju Lu

  • 1Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, United States of America.

Plos Computational Biology
|September 27, 2013
PubMed
Summary

A new quantitative model of channelrhodospin-2 (ChR2) accurately predicts its behavior in cardiac cells. This validated optogenetic tool aids in designing new light-sensitive ion channels for neuroscience and cardiac electrophysiology applications.

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Area of Science:

  • Optogenetics
  • Cardiac Electrophysiology
  • Computational Biology

Background:

  • Channelrhodospin-2 (ChR2) is a vital optogenetic tool for controlling neuronal and cardiac excitability.
  • Accurate ChR2 models are crucial for predicting cellular responses to optical stimulation in silico.
  • Existing models require refinement for precise application in complex biological systems.

Purpose of the Study:

  • To develop and validate an accurate quantitative model of the ChR2 H134R mutant.
  • To characterize ChR2's voltage- and irradiance-dependent behavior.
  • To enable in silico prediction of ChR2 function in various cardiac cell types.

Main Methods:

  • Collected experimental data on ChR2 H134R response to varying irradiance and voltage.
  • Developed a ChR2 model with empirically-derived parameters, optimized using simulated annealing.
  • Validated the model in guinea pig ventricular myocytes using optical action potential clamp.
  • Integrated the model into human ventricular, atrial, and Purkinje cell models.

Main Results:

  • The ChR2 model accurately captures inward rectification, voltage/light-dependent kinetics, and response amplitude/morphology.
  • Model predictions were experimentally validated in guinea pig cardiomyocytes.
  • Human cardiac cells showed differential light sensitivity, with Purkinje cells being most excitable.

Conclusions:

  • The developed ChR2 model provides accurate in silico predictions for optogenetic applications in cardiac tissue.
  • This validated model facilitates the design of ChR2-based tools for neuroscience and cardiac electrophysiology.
  • It enables virtual experimentation at cellular and organ levels, guiding in vivo tool development.